MSKCC has made a major commitment to translational research in prostate cancer, recruited new faculty, constructed new facilities, and provided substantial pilot funding for translational research projects. MSKCC cares for a large population of patients (less than 1400/yr) with all stages of prostate cancer. While ethnic minorities are under represented, the large prostate cancer population assures sufficient minority patients eligible for SPORE investigations. Our strategy is to develop risk-adjusted therapies targeted to the characteristics of individual cancers. Translational research objectives are to: 1) develop predictive models of the natural history of localized cancer to improve patient decision-making and treatment selection, 2) determine critical molecular and genetic mechanisms of progression and metastasis; 3) develop risk-adjusted therapy for progression after local treatment using immunologic (PSMA-targeted vaccines) and other biologic agents; and 4) develop new mechanism-based therapy for advanced cancers. These goals will be addressed through 4 research projects (Population-based study of natural history, Molecular carcinogenesis, DNA vaccines, and Experimental therapeutics) supported by 6 cores (Pathology and tissue bank, Informatics, Animal models, Animal imaging, DNA arrays, and Administration), and Developmental Research (pilot projects) and Career Development components. The applied and basic scientists are organized into 3 multidisciplinary Translational Working Groups: Clinical Outcomes and Prognosis, Molecular Mechanisms and Markers, and Experimental Therapeutics. This SPORE addresses key research priorities of the NCI's Prostate Cancer Progress Review Group: new animal models, molecular mechanisms of carcinogenesis and invasion, validation of prognostic markers, and new targets for therapy. An MSKCC SPORE can provide NCI with a large patient population and frozen tissue bank, a history of active participation in clinical trials, a multidisciplinary team of clinicians and scientists successfully collaborating, an expanding basic research program, and advanced experimental therapeutics. The ultimate goal is to bring basic discoveries regarding mechanisms of prostate cancer development and progression to the clinic. With SPORE support, MSKCC can expand its approaches to the prevention, diagnosis, and treatment of prostate cancer to eventually reduce morbidity and mortality from this disease.